Is CHST3 p.Leu379= (c.1135C>T) pathogenic?

CHST3 p.Leu379= (c.1135C>T) is classified Conflicting classifications of pathogenicity in CHST3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-20). Rare (popmax 0.469%, mid); Associated with spondyloepiphyseal dysplasia with congenital joint dislocations.

What condition is associated with CHST3 p.Leu379= (c.1135C>T)?

CHST3 p.Leu379= (c.1135C>T) is associated with spondyloepiphyseal dysplasia with congenital joint dislocations (ClinVar).

How common is CHST3 p.Leu379= (c.1135C>T) in the general population?

CHST3 p.Leu379= (c.1135C>T) is rare (popmax 0.469%, mid) (gnomAD).

How is CHST3-related skeletal dysplasia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CHST3 p.Leu379=

c.1135C>T · rs564028722 · VCV715153

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.469%, mid)

Conditions

spondyloepiphyseal dysplasia with congenital joint dislocations

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.82, phastCons 1
Overall
CADD	9.568	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.469% Middle Eastern · 24/5,120 alleles

Filtering AF 0.323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.275%

Overall 0.0252% 390/1,548,836 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.469%	213
Ashkenazi Jewishnot grpmax-eligible	0.192%	520
African / African-American	0.0793%	1,261
Admixed American	0.0667%	1,499
Remaining individualsnot grpmax-eligible	0.0567%	1,764
European (non-Finnish)	0.016%	6,231
South Asian	0.00119%	83,976

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CHST3
Protein: p.Leu379=
Coding: c.1135C>T
MANE Select: NM_004273
dbSNP: rs564028722
Type: single nucleotide variant
Location: chr10:72008166 (GRCh38)
Gene constraint: LOEUF 1.119 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.58

Full CHST3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spondyloepiphyseal dysplasia with congenital joint dislocations — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CHST3-related skeletal dysplasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal

Similar variants

CHST3 p.Arg221Cys Pathogenic/Likely pathogenic ★★ same condition
CHST3 p.Glu230Ter Pathogenic/Likely pathogenic ★★ same condition
CHST3 p.Phe159Ile Pathogenic/Likely pathogenic ★★ same condition
CHST3 c.*57G>T Uncertain significance ★★ same condition
CHST3 c.*66G>T Uncertain significance ★★ same condition
CHST3 p.Ala106Thr Uncertain significance ★★ ⚠ same condition
CHST3 p.Ala129Glu Uncertain significance ★★ ⚠ same condition
CHST3 p.Ala182Thr Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/chst3-p-leu379 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown